The evolutionary selective advantage of HIV-1 escape variants and the contribution of escape to the HLA-associated risk of AIDS progression.
HIV-1 escape from surveillance by cytotoxic T lymphocytes (CTL) is thought to cause at least transient weakening of immune control. However, the CTL response is highly adaptable and the long-term consequences of viral escape are not fully understood. The objective of this study was to address the qu...
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Public Library of Science (PLoS)
2008-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003486&type=printable |
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| author | Becca Asquith |
| author_facet | Becca Asquith |
| author_sort | Becca Asquith |
| collection | DOAJ |
| description | HIV-1 escape from surveillance by cytotoxic T lymphocytes (CTL) is thought to cause at least transient weakening of immune control. However, the CTL response is highly adaptable and the long-term consequences of viral escape are not fully understood. The objective of this study was to address the question "to what extent does HIV-1 escape from CTL contribute to HLA-associated AIDS progression?" We combined an analysis of 21 escape events in longitudinally-studied HIV-1 infected people with a population-level analysis of the functional CTL response in 150 subjects (by IFNg ELISpot) and an analysis of the HIV-1 sequence database to quantify the contribution of escape to the HLA-associated rate of AIDS progression. We found that CTL responses restricted by protective HLA class I alleles, which are associated with slow progression to AIDS, recognised epitopes where escape variants had a weak evolutionary selective advantage (P = 0.008) and occurred infrequently (P = 0.017). Epitopes presented by protective HLA class I alleles were more likely to elicit a CTL response (P = 0.001) and less likely to contain sequence variation (P = 0.006). A third of between-individual variation in HLA-associated disease risk was predicted by the selective advantage of escape variants: a doubling in the evolutionary selective advantage was associated with a decrease in the AIDS-free period of 1.2 yrs. These results contribute to our understanding of what makes a CTL response protective and why some individuals progress to AIDS more rapidly than others. |
| format | Article |
| id | doaj-art-3a15ca97de6943bf84afbf34fdf07efa |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-3a15ca97de6943bf84afbf34fdf07efa2025-08-20T02:38:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-01310e348610.1371/journal.pone.0003486The evolutionary selective advantage of HIV-1 escape variants and the contribution of escape to the HLA-associated risk of AIDS progression.Becca AsquithHIV-1 escape from surveillance by cytotoxic T lymphocytes (CTL) is thought to cause at least transient weakening of immune control. However, the CTL response is highly adaptable and the long-term consequences of viral escape are not fully understood. The objective of this study was to address the question "to what extent does HIV-1 escape from CTL contribute to HLA-associated AIDS progression?" We combined an analysis of 21 escape events in longitudinally-studied HIV-1 infected people with a population-level analysis of the functional CTL response in 150 subjects (by IFNg ELISpot) and an analysis of the HIV-1 sequence database to quantify the contribution of escape to the HLA-associated rate of AIDS progression. We found that CTL responses restricted by protective HLA class I alleles, which are associated with slow progression to AIDS, recognised epitopes where escape variants had a weak evolutionary selective advantage (P = 0.008) and occurred infrequently (P = 0.017). Epitopes presented by protective HLA class I alleles were more likely to elicit a CTL response (P = 0.001) and less likely to contain sequence variation (P = 0.006). A third of between-individual variation in HLA-associated disease risk was predicted by the selective advantage of escape variants: a doubling in the evolutionary selective advantage was associated with a decrease in the AIDS-free period of 1.2 yrs. These results contribute to our understanding of what makes a CTL response protective and why some individuals progress to AIDS more rapidly than others.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003486&type=printable |
| spellingShingle | Becca Asquith The evolutionary selective advantage of HIV-1 escape variants and the contribution of escape to the HLA-associated risk of AIDS progression. PLoS ONE |
| title | The evolutionary selective advantage of HIV-1 escape variants and the contribution of escape to the HLA-associated risk of AIDS progression. |
| title_full | The evolutionary selective advantage of HIV-1 escape variants and the contribution of escape to the HLA-associated risk of AIDS progression. |
| title_fullStr | The evolutionary selective advantage of HIV-1 escape variants and the contribution of escape to the HLA-associated risk of AIDS progression. |
| title_full_unstemmed | The evolutionary selective advantage of HIV-1 escape variants and the contribution of escape to the HLA-associated risk of AIDS progression. |
| title_short | The evolutionary selective advantage of HIV-1 escape variants and the contribution of escape to the HLA-associated risk of AIDS progression. |
| title_sort | evolutionary selective advantage of hiv 1 escape variants and the contribution of escape to the hla associated risk of aids progression |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003486&type=printable |
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